Abstract
Immunoglobulin A (IgA) is generated in the gut by both T cell-dependent and T cell-independent processes. The sites and the mechanisms for T cell-independent IgA synthesis remain elusive. Here we show that isolated lymphoid follicles (ILFs) were sites where induction of activation-induced cytidine deaminase (AID) and IgA class switching of B cells took place in the absence of T cells. We also show that formation of ILFs was regulated by interactions between lymphoid tissue-inducer cells expressing the nuclear receptor ROR gamma t (ROR gamma t(+)LTi cells) and stromal cells (SCs). Activation of SCs by ROR gamma t(+)LTi cells through lymphotoxin (LT)-beta receptor (LT beta R) and simultaneously by bacteria through TLRs induced recruitment of dendritic cells (DCs) and B cells and formation of ILFs. These findings provide insight into the crosstalk between bacteria, ROR gamma t(+)LTi cells, SCs, DCs, and B cells required for ILF formation and establish a critical role of ILFs in T cell-independent IgA synthesis in gut.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Cell Communication
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Cytidine Deaminase / metabolism
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Cytokines / immunology
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Cytokines / metabolism
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Gastrointestinal Tract / immunology*
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Gastrointestinal Tract / metabolism
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Immunoglobulin A / biosynthesis*
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Immunoglobulin A / immunology
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Immunoglobulin Class Switching
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Lymphoid Tissue / cytology
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Lymphoid Tissue / immunology*
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Lymphoid Tissue / metabolism
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Lymphotoxin beta Receptor / immunology
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Lymphotoxin beta Receptor / metabolism
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Mice
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Mice, Knockout
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Mice, Mutant Strains
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Retinoic Acid / metabolism
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Receptors, Thyroid Hormone / metabolism
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Stromal Cells / immunology
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Stromal Cells / metabolism
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
Substances
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Cytokines
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Immunoglobulin A
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Lymphotoxin beta Receptor
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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Rorc protein, mouse
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Cytidine Deaminase